For the purpose of investigating the role of the mixed infection with both aerobic and anaerobic bacteria on the formation of lung abscess, experimental lung abscess was produced by inoculating intrabronchially both Staphylococcus aureus and Bacteroides fragilis mixed with Freund's incomplete adjuvant through a tube insertedperorally to one site of the lung of a rabbit which had been sensitized with mixture of killed S.aureus and Freund's incomplete adjuvant.
After the inoculation, morphological and bacteriological findings of lung abscess were investigated at several times.
The results were compared with those of lung abscess due to S.aureus alone and due to S.aureus and Klebsiella pneumoniae mixed, and investigated the effects of penicillin G and lincomycin administration.
The results obtained were as follows.
1) In rabbits inoculated with 10⁹ CFU of S.aureus and 10³ CFU of B.fragilis, lung abscess formation was observed in 78.8% of them. Lesions due to S.aureus and B.fragilis were larger than those due to S.aureus alone and those due to S.aureus and K.pneumoniae.
2) Viable cells of both S.aureus and B.fragilis in lesion increased in two weeks after inoculation, and as time passed by, gradually decreased.The tendency was observed that the cells of B.fragilis decreased faster than those of S.aureus.
3) In the group of lincomycin administration, viable cells of both S.aureus and B.fragilis in the lesions eliminated fastly.In the group of penicillin G administration, viable cells of B.fragilis decreased with that of S.aureus decreasing.Those results demonstrated that viable cells of B.fragilis in lesions increased as symbiote of S.aureus and contributed to enlargement of lesions.

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Pharmacokinetic study of cefotaxime (CTX) after intravenous injection was carried out in patients with various degrees of renal function.
Serum CTX concentrations were determined by the thin-layer cup method using Bacillus subtilis ATCC 6633 as the test organism.Pharmacokinetic analyses were performed by the two-compartment open model.
In patients with various degrees of renal impairment, serum levels and half-lives were inversely correlated with Ccr.Serum concentrations and half-lives were not significantly affected by dialysis except in a group of patients (Ccr 5-3ml/min), which showed lowering of these parameters.

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Penetration of ceftazidime (CAZ) into wound exudate after MILES operation was studied clinically. One or 2g of CAZ was administered to 9 patients, twice a day intravenously.Drainage tube, inserted into the dead space of the pelvic cavity, was suctioned continuously (-15cm H₂O). Wound exudate was collected daily, and on every 30 or 60 minutes on the first postoperative day.The concentration of CAZ was measured by thin layer disc method, and the results were corrected by the body weight of each patient.
The volume of wound exudate of the operative day (299ml) was significantly more than that of the first (148ml), the second (66ml), the third (42ml) and the fourth (42ml) postoperative day (P<0.001).The concentration of hemoglobin in wound exudate of the operative day (2.6g/dl) was significantly higher than that of the first (0.7g/dl), the second (0.4g/dl), the third (0.5g/dl) and the fourth (0.4g/dl) postoperative day (P<0.01).The concentration of albumin in wound exudate showed little change during 5 days after operation.
The daily concentration of CAZ in wound exudate was 20.1μg/ml (2g-2/day) and 9.97μg/ml (1g-2/day), and showed little change during 5 days after operation.The maximum concentration and the area under the curve of CAZ in wound exudate was 52.4μg/ml, 388.6hr·μg/ml (2g iv) and 22.7g/ml, 162.9hr·μg/ml (1g iv).That is, the more the dose of administration of CAZ was, the higher the concentration of CAZ in wound exudate was.The time-concentration curve of CAZ in wound exudate was gently-sloping;2.6-4.7 hours was needed to reach the peak, and the half life of CAZ was 2.0-2.1 hours.The level of CAZ was maintained higher than 25μg/ml (2g iv) or 12.5g/ml (1g iv) for 6 hours.So, it was expected that CAZ might prevent the breakout of postoperative infections, at a dose of 1g, twice a day.These results were equal to those of previous reports in which penetration of CAZ into wound exudate after radical mastectomy was studied.
In a case with chronic renal failure, the peak level of CAZ in wound exudate was equal to those of other cases.But, because of its long half life (3.00 hours), the area under the curve of CAZ in the patient with chronic renal failure was 1.7 times as high as those of other cases.

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Cefoperazone (CPZ) was administrated to 37 patients undergone biliary surgery to prevent postoperative biliary infection.CPZ moved over to the bile, the liver and the gall bladder wall in high concentration after 2g administration intravenously.Mean concentration of CPZ in the bile in the common bile duct, bile in the gall bladder, in the liver and in the gall bladder wall were 1, 538μg/ml, 238.3μg/ml, 209.1μg/g and 158.1μg/g respectively. Peak concentration of CPZ in the liver was demonstrated at 90 minutes after injection.Elevation of serum GOT and GPT was observed in high incidence in this study but there was no serious postoperative complication or biliary infection.High concentration of CPZ in the bile and other results suggested usefulness of CPZ for biliary surgery patients.

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The results described below were obtained by a combination therapy study group which was organized to evaluate the efficacy and safety of the new monobactam antibiotic azthreonam (AZT) used in combination with clindamycin (CLDM) in the treatment of respiratory infections.
[Experimental findings]
1.Antimicrobial activity: AZT, when used in combination with CLDM, showed antimicrobial activity against all 32 standard strains of gram-negative or positive organisms, resulting in an enlargement of its antimicrobial spectrum.The combined use of the two drugs resulted in a slight summation or potentiation in the case of S.aureus, E.coil, K.pneumoniae and E.cloacas, while a well-defined potentiation was observed with S.marcescens.An antagonistic effect was produced against most of the P.aeruginosa strains.
2.Effects of the combination on each drug: An unpleasant smell was noted for CLDM upon dissolution. However, the combination resulted in no changes in color or potency of either drug.
[Clinical findings]
As a rule, 1g×2/day of AZT and 600mg×2/day of CLDM were administered to inpatients withwell-defind respiratory infections.The drugs were administered either separately or as a mixture by D.I.Treatment was continued for 7 to 14 days.
1. Of the 102 enrolled cases of respiratory infections, 90 were retained for evaluation of the clinical efficacy.
2. Of the 90 retained patients, 60 were males and 30 females.Sixty-one patients (67.8%) were aged 60 and over and 69 (76.7%) had underlying diseases, which were moderate or severe in 56 cases (62.2%). Infections were found to be moderate or severe in 81 cases (93.1%, if calculated excluding 3 unknown cases).Infections were thus severe or refractory in a great majority of patients.
3.The combination therapy was found to be effective in 20 of 30 cases (66.7%) of chronic respi ratory tract infections, in 28 of 45 cases (62.2%) of pneumonia and in 8 of 9 cases (88.9%) of suppurative diseases of the lung, resulting in an efficacy rate of 66.7%(60/90 cases) on the whole.
4.The efficacy rate was 76.2%(16/21 cases) and 63.8%(44/69 cases) in the absence and presence of underlying diseases, respectively.The difference between the two rates was statistically significant.
5.The combination therapy was found to be effective in 15 of 26 cases (57.7%) where only gramnegative rods were isolated and 70.0%(7/10 cases) were only gram-positive cocci were isolated. Two or more organisms were detected in 15 cases for which an efficacy rate of 66.7%(10 cases) was obtained.
6.The combination therapy eradicated 37 of 44 (84.1%) strains of gram-negative rods and 12 of 14 (85.7%) of gram-positive cocci, resulting in an eradication rate of 85.5%(53/62 trains) on the whole.The microbiological efficacy rates were thus higher than the clinical efficacy rates.
7. Side effects occurred in 15 cases, including rash or skin eruption in 7, diarrhea in 2 and bitter taste in 3. One patient had facial edema, flushing and hypotension which seemed to be associated with CLDM and probably with an accelerated rate of infusion.These symptoms subsided promptly upon discontinuation of the treatment.
8.Major abnormal laboratory findings were transient elevations in S-GOT and S-GPT. Eosinophils also elevated in a few cases.The incidence of abnormal laboratory findings was relatively high (31.4% or 32/102 cases).
9.The attending physicians evaluated the combination “very useful” in 7 cases, “useful” in 43, slightly useful in 26, “not useful” in 18 and “unknown” in 8.

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